During the early years of this project, the Neuropathology Core established a new neuropathology laboratory, perfected histopathological techniques, and applied these to cases of Alzheimers disease and other dementias acquired from the hospitals we serve and from the community at large. Over the past 5 years, our "Rapid Autopsy Protocol" recovered 45 cases with postmortem intervals of less than six hours. We have provided tissue for investigators of the Center as well as for others. We now build upon these strengths by adding Dr. Alden Dudley and the CA Medical Center to expand our autopsy services. New projects began last spring with the study of microglia by Dr. Dana Giulian and co-workers, which has developed into Project 3. We have established collaboration with Dr. Alex Roher of Wayne State University who will extract our specimens to obtain native amyloid and senile plaque proteins for studies of their effects on neuronal death (Project 1) and microglial reactivity (Project 3). Dr. Lanny Haverkamp, a histologist and neurobiologist, has joined the core facility and will apply confocal laser microscopy to quantitate relationships among plaque types, glial reactivity and synaptic loss. Dr. Hannes Vogel, a neuropathologist, has also become a member of the core and will examine the expression of adhesion molecules in Alzheimer's disease. Drs. Dudley and Vogel, as board-certified neuropathologists, will strengthen the pathology service in performance of timely autopsies in carefully studied patients from the Clinical Core, which have already begun to increase. With these plans, extensively revised from the previous application, we will continue to sere our classic role of histopathologic diagnosis, and also will interact with multiple facets of the Center in projects which are scientifically sound and creative.